Diethyl Ether → (S)-1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethanamine

HRID 1842438Notes

Reaction equation

HRID 1842438 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:19](=[S:21])[NH2:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)(C)(C)C.Br[CH2:24][C:25](=O)[CH2:26][CH3:27].C(OCC)C>CC#N>[CH2:26]([C:25]1[N:20]=[C:19]([C@@H:8]([NH2:7])[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=2)[S:21][CH:24]=1)[CH3:27]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 131561-Bromo-2-butanoneHCID 57943188[2-(4-nitrophenyl)-1-(S)-thiocarbamoylethyl]carbamic acid tert-butyl ester

Product 1

HCID 57943187(S)-1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethanamineYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of [2-(4-nitrophenyl)-1-(S)-thiocarbamoylethyl]-carbamic acid tert-butyl ester, 2, (0.245 g, 0.753 mmol), 1-bromo-2-butanone (0.125 g, 0.828 mmol) in CH3CN (5 mL) is refluxed 3 hours. The reaction mixture is cooled to room temperature and diethyl ether is added to the solution and the precipitate which forms is removed by filtration. The solid is dried under vacuum to afford 0.242 g (90% yield) of the desired product. ESI+MS 278 (M+1). Preparation of {1-[1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethylcarbamoyl]-2-phenylethyl}carbamic acid tert-butyl ester (4): To a solution of 1-(S)-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethyl amine hydrobromide, 3, (0.393 g, 1.1 mmol), (S)-(2-tert-butoxycarbonylamino)-3-phenylpropionic acid (0.220 g, 0.828 mmol) and 1-hydroxybenzotriazole (HOBt) (0.127 g, 0.828 mmol) in DMF (10 mL) at 0° C., is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (0.159 g, 0.828 mmol) followed by diisopropylamine (0.204 g, 1.58 mmol). The mixture is stirred at 0° C. for 30 minutes then at room temperature overnight. The reaction mixture is diluted with water and extracted with EtOAc. The combined organic phase is washed with 1 N aqueous HCl, 5% aqueous NaHCO3, water and brine, and dried over Na2SO4. The solvent is removed in vacuo to afford 0.345 g of the desired product which is used without further purification. LC/MS ESI+525 (M+1).

Workup

  1. temperatureis refluxed 3 hours
  2. customthe precipitate which forms is removed by filtration
  3. customThe solid is dried under vacuum

Sources & evidence

ORD record
ord-83c505384eec413096f47c045c24785e
Source dataset
uspto-grants-2015_02
Patent number
US08946232B2

Reaction notes

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